The Influenza A virus, which belongs to the Orthomyxoviridae family, can cause influenza in humans, birds or domesticated food animals. The virus can be classified into different subtypes based on their surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Of the 16 known HAs and nine NAs, three HA subtypes (H1, H2, and H3) and two NA subtypes (N1 and N2) are most commonly found in humans. H1N1 and H3N2 are the major subtypes that cause human seasonal flu and global pandemics of influenza. The influenza pandemic in 2009 was caused by influenza A virus H1N1 of swine origin. This has led to a growing concern regarding the pandemic potential of the highly pathogenic avian influenza H5N1 viruses. Thus the development of an effective and safe vaccine against divergent influenza A virus strains is urgently needed for the prevention of future outbreaks of influenza.
Neutralizing monoclonal antibodies (MAbs), particularly those having cross-clade neutralizing activity, play a critical role in immunoprotection against various influenza A virus (IAV) infections, particularly those caused by the highly pathogenic avian influenza H5N1 virus and any future unpredictable virus strains.
Although vaccination is an important strategy to prevent influenza infection, most of the current vaccines cannot provide immediate protection in the event of influenza pandemics and epidemics due to the length of time required for producing effective vaccines. Furthermore, these vaccines are limited to one or just a few strains and don't produce highly potent neutralizing antibodies or cross-reactive immunity against divergent influenza viruses. Neutralizing antibodies can provide a first line of defense against influenza pathogens and passive immunization with neutralizing MAbs can provide immediate effects to prevent the spread of influenza infection and mortality. However, it has been difficult to obtain MAbs which neutralize divergent strains of influenza viruses with sufficient cross-protective immunity.